POLERISE
Research type
Research Study
Full title
A phase Ib/IIa clinical trial to combine the CSF1 receptor inhibitor pexidartinib with the androgen receptor antagonist enzalutamide in metastatic castration resistant prostate cancer
IRAS ID
213217
Contact name
Simon Crabb
Contact email
Sponsor organisation
University Hospital Southampton NHS Trust
Eudract number
2016-003291-47
Duration of Study in the UK
2 years, 10 months, 1 days
Research summary
Over 40,000 men are diagnosed with prostate cancer and over 10,000 die from advanced metastatic disease annually in the UK. Initial treatment of metastatic disease is with androgen deprivation therapy (ADT). Although 80-90% respond, subsequent disease progression (termed metastatic castration resistant prostate cancer, mCRPC) occurs in virtually all patients at a median somewhere between 6 to 26 months.
Many patients who develop mCRPC will receive hormonal therapy with enzalutamide. Despite the survival and quality of life benefits achieved with enzalutamide, subsequent disease progression is effectively inevitable for all patients because of treatment resistance.
Both clinical and pre-clinical data exist to suggest that enzalutamide resistance may be linked to immune cell infiltration by macrophages, driven by prostate cancer cell expression of stimulatory cytokines including colony stimulating factor 1 (CSF1).
Pexidartinib is a CSF1 inhibitor which will be added to enzalutamide treatment in this trial. This trial will take place in four NHS trusts and is looking to recruit a maximum of 65 patients (expanding to 90 if a second dose expansion phase is undertaken).
The dose escalation phase will follow a rolling six (3+3) design in advanced patients who are either naïve or resistant to enzalutamide. There will be five dose levels of Pexidartinib. Patients will receive cycle of Pexidartinib on a 28 day cycle schedule until progression occurs.
Once a recommended phase II dose has been determined the trial will open into a single arm phase II expansion, investigating the recommended phase II dose in combination with enzalutamide in enzalutamide resistant patients. However, if a biologically effective dose is determined to be lower than the maximal tolerated dose, there is the option to explore two doses in a randomised phase 2 expansion.
If results from the phase 2 are positive, we will progress to a phase III trial.
REC name
West Midlands - Coventry & Warwickshire Research Ethics Committee
REC reference
16/WM/0480
Date of REC Opinion
25 Jan 2017
REC opinion
Further Information Favourable Opinion